The DPT-1 is a nationwide study to determine if insulin-based therapies can delay or prevent the clinical onset of Type 1 diabetes in relatives found to be at high risk of development of the disease. Parental insulin is used in relatives with >50% projected 5-year risk. Oral insulin is used in relatives with 26 to 50% projected 5-year risk. Screening began in February 1994. Randomization began in December of 1995 for the Parenteral Protocol and in September, 1996 for the Oral Protocol. By December 31, 1999 there were 79,521 samples received for screening of which 74,573 (94%) were eligible. Of the 79,521 samples analyzed for islet cell antibodies (ICA) by 12/31/99, 2849 were positive. The rate of positive samples, 3.82%, is a rate higher than projected in calculating sample size (3.6%). Of the 1972 individuals who were staged for risk, 489 (24.8%) had low first phase insulin response (FPIR) to IVGTT and 1483 (75.2%) had normal FPIR to IVGTT. Of the subject's who completed staging for risk categorization, 325 were eligible for the Parenteral Study, and of these 295 were randomized. Of the 254 subjects eligible for the Oral Study, 247 were randomized. Overall enrollment rates are (66%) of the projected for the Parenteral Study, and (53%) of the projected for the Oral Study by this point in time.